DOI QR코드

DOI QR Code

Investigation of ICAM-1 and β3 Integrin Gene Variations in Patients with Brain Tumors

  • Yilmaz, Umit (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Zeybek, Umit (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Kahraman, Ozlem Timirci (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Kafadar, Ali Metin (Department of Neurosurgery, Cerrahpasa Faculty of Medicine, Istanbul University) ;
  • Toptas, Bahar (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Yamak, Nesibe (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Celik, Faruk (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University) ;
  • Yaylim, Ilhan (Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University)
  • Published : 2013.10.30

Abstract

Background: Primary brain tumors constitute a small percent of all malignant cancers, but their etiology remains poorly understood. ${\beta}3$ integrin (ITGB3) has been recognized to play influential roles in angiogenesis, tumor growth and metastasis. Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein important for tumor invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and ITGB3 could be associated with brain cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between brain tumor risk and ICAM-1 and ${\beta}3$ integrin gene polymorphisms. Materials and Methods: The study covered 92 patients with primary brain tumors and 92 age-matched healthy control subjects. Evaluation of ${\beta}3$ integrin (Leu33Pro (rs5918)) and ICAM-1 (R241G (rs1799969) and K469E (rs5498)) gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: According to results of our research, the A allele of the ICAM-1 R241G gene polymorphism appeared to be a risk factor for primary brain tumors (p<0.001). Similarly, the frequency of the A mutant allele of ICAM-1 R241G was statistically significant in patients with brain tumors classified as glioma (p<0.001). When allele and genotype distributions of ICAM-1 K469E, ICAM-1 R241G and ${\beta}3$ integrin Leu33Pro gene polymorphisms were evaluated with age, sex, and smoking, there were no statistically significant differences. Haplotype analysis revealed that the frequencies of GAC (rs1799969-rs5498-rs5918) and GAT (rs1799969-rs5498-rs5918) haplotypes were significantly lower in patients as compared with controls (p=0.001; p=0.036 respectively). Conclusions: This study provides the first evidence that ICAM-1 R241G SNP significantly contributes to the risk of primary brain tumors in a Turkish population. In addition, our results suggest that ICAM-1 R241G in combination ICAM-1 K469E may have protective effects against the development of brain cancer.

Keywords

Cancer;brain tumor;polymorphism;ICAM-1;${\beta}3$-integrin

References

  1. Alexiou D, Karayiannakis AJ, Syrigos KN, et al (2003). Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients. Am J Gastroenterol, 98, 478-85. https://doi.org/10.1111/j.1572-0241.2003.07259.x
  2. Arandi N, Talei A, Erfani N, et al (2008). Intercellular adhesion molecule-1 genetic markers (+241G/A and +469A/G) in Iranian women with breast cancer. Cancer Genetics and Cytogenetics, 183, 9-13. https://doi.org/10.1016/j.cancergencyto.2008.01.019
  3. Bojesen SE, Tybjaerg-Hansen A, Nordestgaard BG (2003). Integrin beta3 Leu33Pro homozygosity and risk of cancer. J Natl Cancer Inst, 95, 1150-7. https://doi.org/10.1093/jnci/djg005
  4. Brand RE, Nolen BM, Zeh HJ, et al (2011). Serum biomarker panels for the detection of pancreatic cancer. Clin Cancer Res, 17, 805-16. https://doi.org/10.1158/1078-0432.CCR-10-0248
  5. Cox DG, Hankinson SE, Hunter DJ (2006). Polymorphisms in the ICAM gene locus are not associated with breast cancer risk. Cancer Epidem Biomar Prev, 15, 178-9. https://doi.org/10.1158/1055-9965.EPI-05-0790
  6. Brooks PC, Clark RA, Cheresh DA (1994). Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science, 264, 569-71. https://doi.org/10.1126/science.7512751
  7. Burgess K (2010). Rehabilitation for brain tumour patients: Why not? A neuroscience nurse perspective. Aust J Neur, 20, 20-6.
  8. Burim RV, Teixeira SA, Colli BO, et al (2009). ICAM-1 (Lys469Glu) and PECAM-1 (Leu125Val) polymorphisms in diffuse astrocytomas. Clin and Experimental Med, 9, 157-63. https://doi.org/10.1007/s10238-009-0040-6
  9. D'Abaco GM, Kaye AH (2007). Integrins: molecular determinants of glioma invasion. J Clin Neurosci, 14, 1041-8. https://doi.org/10.1016/j.jocn.2007.06.019
  10. Demuth T, Berens ME (2004). Molecular mechanisms of glioma cell migration and invasion. J Neuro Oncol, 70, 217-28. https://doi.org/10.1007/s11060-004-2751-6
  11. Dietrich J-B (2002). The adhesion molecule ICAM-1 and its regulation in relation with the blood-brain barrier. J Neuroimmunol, 128, 58-68. https://doi.org/10.1016/S0165-5728(02)00114-5
  12. Eggeman H, Stoblen F, Thill M, et al (2011). Influence of a dose-dense adjuvant chemotherapy on sVCAM-1/sICAM-1 serum levels in breast cancer patients with 1-3 positive lymph nodes. Anticancer Res, 31, 2617-22.
  13. Felding-Habermann B, Fransvea E, O'Toole TE, et al (2002). Involvement of tumor cell integrin alpha v beta 3 in hematogenous metastasis of human melanoma cells. Clin Exp Metastas, 19, 427-36. https://doi.org/10.1023/A:1016377114119
  14. Felding-Habermann B, O'Toole TE, Smith JW, et al (2001). Integrin activation controls metastasis in human breast cancer. Proc Natl Acad Sci USA, 98, 1853-8. https://doi.org/10.1073/pnas.98.4.1853
  15. Gogali A, Charalabopoulos K, Zampira I, et al (2010). Soluble adhesion molecules E-cadherin, intercellular adhesion molecule-1, and E-selectin as lung cancer biomarkers. CHEST J, 138, 1173-9. https://doi.org/10.1378/chest.10-0157
  16. Fisher JL, Schwartzbaum JA, Wrensch M, et al (2007). Epidemiology of brain tumors. Neurologic Clin, 25, 867-90. https://doi.org/10.1016/j.ncl.2007.07.002
  17. Fischer U, Meese E (2007). Glioblastoma multiforme: the role of DSB repair between genotype and phenotype. Oncogene, 26, 7809-15. https://doi.org/10.1038/sj.onc.1210878
  18. Giles GG, Gonzales MF, Kaye HA (2001). Brain tumors. 2 edn. Churchill-Livingstone, London
  19. Gu J, Liu Y, Kyritsis AP, Bondy ML (2009). Molecular epidemiology of primary brain tumors. Neurotherapeutics, 6, 427-35. https://doi.org/10.1016/j.nurt.2009.05.001
  20. Hood JD, Cheresh DA (2002) Role of integrins in cell invasion and migration. Nature Reviews Cancer, 2, 91-100. https://doi.org/10.1038/nrc727
  21. Howell WM, Rose-Zerilli MJ, Theaker JM, et al (2005). ICAM-1 polymorphisms and development of cutaneous malignant melanoma. Int J Immunogenet, 32, 367-73. https://doi.org/10.1111/j.1744-313X.2005.00539.x
  22. Iwao M, Morisaki H, Morisaki T (2004). Single-nucleotide polymorphism g.1548G>A (E469K) in human ICAM-1 gene affects mRNA splicing pattern and TPA-induced apoptosis. Biochem Bioph Res Commun, 317, 729-35. https://doi.org/10.1016/j.bbrc.2004.03.101
  23. Kammerer S, Roth RB, Reneland R, et al (2004). Large-scale association study identifies ICAM gene region as breast and prostate cancer susceptibility locus. Cancer Res, 64, 8906-10. https://doi.org/10.1158/0008-5472.CAN-04-1788
  24. Kargiotis O, Rao JS, Kyritsis AP (2006). Mechanisms of angiogenesis in gliomas. J Neuro Oncology, 78, 281-93. https://doi.org/10.1007/s11060-005-9097-6
  25. Langsenlehner U, Renner W, Yazdani-Biuki B, et al (2006). Integrin alpha-2 and beta-3 gene polymorphisms and breast cancer risk. Breast Cancer Res Treat, 97, 67-72. https://doi.org/10.1007/s10549-005-9089-4
  26. Moriyama M, Matsumura H, Shioda J, et al (2006). Measurement of human intercellular adhesion molecule 1 in the blood is useful for predicting the occurrence of hepatocellular carcinomas from chronic hepatitis c and liver cirrhosis. Intervirol, 49, 327-38 https://doi.org/10.1159/000095152
  27. Lee EB, Kim JY, Kim EH, et al (2004). Intercellular adhesion molecule-1 polymorphisms in Korean patients with rheumatoid arthritis. Tissue Antigens, 64, 473-7. https://doi.org/10.1111/j.1399-0039.2004.00285.x
  28. Louis DN, Scheithaur BW, Budka H, et al (2000). Meningiomas. WHO classification of tumour: pathology and genetics of tumoursof the nervous system. 3 edn. IARC Press, Lyon
  29. Macchioni P, Boiardi L, Casali B, et al (2000). Intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms in Italian patients with rheumatoid arthritis. Clin Exp Rheumatol, 18, 553-8.
  30. Nakata B, Hori T, Sunami T, et al (2000). Clinical significance of serum soluble intercellular adhesion molecule 1 in gastric cancer. Clin Cancer Res, 6, 1175-9.
  31. Parkin DM, Stiller CA, Draper GJ (1998). The international incidence of childhood cancer. Int J Cancer, 42, 511-20.
  32. Ruddon RW (2007). Cancer Biology. 4 edn. Oxford University Press, New York.
  33. Salvarani C, Casali B, Boiardi L, et al (2000). Intercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell arteritis: association with disease risk and severity. J Rheumatol, 27, 1215-21.
  34. Sims TN, Dustin ML (2002) The immunological synapse: integrins take the stage. Immunological Reviews, 186, 100-17. https://doi.org/10.1034/j.1600-065X.2002.18610.x
  35. Stenberg SS (1997). Central Nervous System. Histology for Pathologists. 2 edn. Lippincott Williams & Wilkins, Philadelphia
  36. Trikha M, Zhou Z, Timar J, et al (2002). Multiple roles for platelet GPIIb/IIIa and alphavbeta3 integrins in tumor growth, angiogenesis, and metastasis. Cancer Res, 62, 2824-33.
  37. Thanopoulou E, Kotzamanis G, Pateras IS, et al (2012). The single nucleotide polymorphism g.1548A >G (K469E) of the ICAM-1 gene is associated with worse prognosis in nonsmall cell lung cancer. Tumour Biol, 33, 1429-36. https://doi.org/10.1007/s13277-012-0393-4
  38. Theodoropoulos G, Papaconstantinou I, Felekouras E, et al (2006). Relation between common polymorphisms in genes related to inflammatory response and colorectal cancer. World J Gastroenterol, 12, 5037-43.
  39. Tian MM, Sun Y, Li ZW, et al (2012). Polymorphisms of ICAM-1 are associated with gastric cancer risk and prognosis. World J Gastroenterol, 18, 368-74. https://doi.org/10.3748/wjg.v18.i4.368
  40. Vijayan KV, Liu Y, Dong JF, et al (2003) Enhanced activation of mitogen-activated protein kinase and myosin light chain kinase by the Pro33 polymorphism of integrin beta 3. J Biol Chem, 278, 3860-7. https://doi.org/10.1074/jbc.M208680200
  41. Vigano P, Infantino M, Lattuada D, et al (2003). Intercellular adhesion molecule- 1 (ICAM-1) gene polymorphisms in endometriosis. Mol Hum Reprod, 9, 47-52. https://doi.org/10.1093/molehr/gag002
  42. Vinceti M, Pellacani G, Casali B, et al (2006). High risk of cutaneous melanoma amongst carriers of the intercellular adhesion molecule-1 R241 allele. Melanoma Res, 16, 93-6. https://doi.org/10.1097/01.cmr.0000198450.19204.dd
  43. Wang-Gohrke S, Chang-Claude J (2005) Re: integrin ${\beta}3$ Leu33Pro homozygosity and risk of cancer. J Natl Cancer Inst, 97, 778-9.
  44. Wang QL, Li BH, Liu B, et al (2009). Polymorphisms of the ICAM-1 exon 6 (E469K) are associated with differentiation of colorectal cancer. J Exp Clin Canc Res, 28, 139. https://doi.org/10.1186/1756-9966-28-139
  45. Weiss LA, Kosova G, Delahanty RJ, et al (2006). Variation in ITGB3 is associated with whole-blood serotonin level and autism susceptibility. Eur J Hum Genet, 14, 923-31. https://doi.org/10.1038/sj.ejhg.5201644
  46. Wrensch M, Fisher JL, Schwartzbaum JA, et al (2005). The molecular epidemiology of gliomas in adults. Neur Focus, 19, 5.

Cited by

  1. Application of Computed Tomography for Differential Diagnosis of Glioma Stoke and Simple Cerebral Hemorrhage vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3425
  2. Impacts of ICAM-1 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan vol.35, pp.8, 2014, https://doi.org/10.1007/s13277-014-1934-9
  3. Clinicopathological Findings and Five Year Survival Rates for Patients with Central Nervous System Tumors in Yazd, Iran vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10319
  4. Association of intercellular adhesion molecule-1 single nucleotide polymorphisms with hepatocellular carcinoma susceptibility and clinicopathologic development vol.37, pp.2, 2016, https://doi.org/10.1007/s13277-015-3992-z